Epstein-Barr virus (EBV) is the aetiological agent of infectious mononucleosis (IM) and is associated with Burkitt's lymphoma (BL), nasopharyngeal carcinoma (NPC) and EBV-associated large cell lymphomas in immunocompromised individuals. Following primary infection, EBV persists for life in B lymphocytes in all healthy seropositive individuals. There is now compelling evidence that persistently infected B lymphocytes are controlled by EBV-specific CTL. This evidence is based on an in vitro model involving CTL and EBV transformed lymphoblastoid cell lines (LCL). It is quite clear that the interaction between these CTL and their target in vivo form the key to tipping the balance in favour of health vs disease. Central to understanding EBV pathogenesis is the notion that EBV-specific CTL have distinct roles in each EBV- associated disease. The new grant will focus on key features which are considered vital for developing our understanding of these roles. 1. The role of transport associated proteins (TAP) in the escape of tumour cells from CTL recognition. Some BL cells appear to have a TAP deficiency which would render them insensitive to CTL attack. The new proposal seeks to determine whether this represents a universal lesion associated not only with BL but also with other human tumours. Methodology to be used includes transfection of CTL epitopes and TAP genes into CTL resistant tumour cells. TAP gene expression will be assessed by Northern analysis and CTL recognition. 2. Sequencing T cell receptors (TcR). The analysis of TcR sequences in this proposal will provide a molecular basis for understanding TcR- peptide/MHC interactions and how they influence CTL specificity for peptide epitope. This knowledge will find application in the analysis of nature of the oligoclonal T cell response involved in acute IM. Methodology will include inverse PCR, replacement net analysis and T cell cloning.